Requirement of the human T-cell leukemia virus (HTLV-1) tax-stimulated HIAP-1 gene for the survival of transformed lymphocytes

Human T cell leukemia virus type 1 (HTLV-1), the cause of adult T cell leukemia (ATL), induces clonal expansion of infected T-cells in nonleukemic individuals and immortalizes T cells in vitro. The resistance against apoptotic stimuli of these cells hints at a viral survival function in addition to a proliferation-stimulating activity. Here we describe the up-regulation of the antiapoptotic HIAP-1/CIAP-2 gene as a consistent phenotype of HTLV-1-transformed and ATL-derived cultures and its stimulation by the viral oncoprotein Tax. Cotransfections revealed a 60-fold increase of HIAP-1 promoter activity mediated by Tax mainly via nuclear factor-kappaB (NF-kappaB) activation. To address the relevance of virally increased HIAP-1 levels for the survival of HTLV-1-transformed cells, its expression was RNA interference (RNAi) suppressed using a lentiviral transduction system. This resulted in a dramatic reduction of cell growth, a strong induction of apoptosis rates, and increased caspases 3/7 activity, which is known to be suppressed by HIAP-1. Thus, the Tax-mediated HIAP-1 overexpression is required to suppress endogenous apoptosis and, therefore, is essential for the survival of HTLV-1-transformed lymphocytes. Moreover, this points to HIAP-1 as an important target of the HTLV-1-mediated NF-kappaB activation.     

Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy.

BACKGROUND: To examine whether systemic diseases like diabetes and arterial hypertension, which frequently cause retinopathies leading to blindness effect the morphology of retinal ganglion cells (RGC). METHODS: Histological retina material with a history of being untreated, or laser-coagulated (LC) diabetic retinopathy (DR), or arterial hypertensive retinopathy (AHR) was used. The RGC were labeled by introducing crystals of the fluorescent carbocyanine dye DiI into the nerve fiber layer, which contains ganglion cell axons. RESULTS: The typical silhouettes of both major types of RGC, parasol and midget cells, were identified. The axons in DR and AHR retinas showed morphology changes such as irregular swelling and beading. Dendritic field sizes were significantly reduced in RGC of both the hypertonic and diabetic retinas. A significant reduction in branching frequency was evident in both the diabetic and hypertonic retinas, in both the midget and the parasol cells. In LC retinas, both parasol and midget RGC were observed within the LC spots, although their numbers were dramatically decreased compared with normal retinas. CONCLUSIONS: The data suggest that diabetes and arterial hypertonia have similar effects on the morphology of RGC, in addition to causing microvascular alterations and bleeding. Therefore, therapeutic measures and prognostic outcomes in diabetic and hypertensive retinopathy should also consider regressive changes in retinal neurons.     

Diagnostic odyssey of a cutaneous mycobacteriosis rare in central Europe

Cutaneous infection with Mycobacterium chelonae is an uncommon disease, although this atypical mycobacterium is an acid-fast bacillus ubiquitous in the environment. It is often misdiagnosed and treated as a fungal or common bacterial infection. We report a case of disseminated atypical mycobacterial skin infection of a 72-year-old woman who was treated with different topical and systemic antimycotic and antibiotic drugs over a period of 5 months without remarkable improvement. Eventually, repeated tissue cultures on special medium and performance of PCR led to the diagnosis of M. chelonae infection. The patient was treated successfully with oral clarithromycin within 8 weeks. In case of abscessing cutaneous infection, M. chelonae should be considered in the differential diagnosis of prolonged disease when common antibiotics are not effective after 2-4 weeks of treatment.     

The endophytic fungus Piriformospora indica reprograms barley to salt-stress tolerance, disease resistance, and higher yield

Disease resistance strategies are powerful approaches to sustainable agriculture because they reduce chemical input into the environment. Recently, Piriformospora indica, a plant-root-colonizing basidiomycete fungus, has been discovered in the Indian Thar desert and was shown to provide strong growth-promoting activity during its symbiosis with a broad spectrum of plants. Here, we report on the potential of P. indica to induce resistance to fungal diseases and tolerance to salt stress in the monocotyledonous plant barley. The beneficial effect on the defense status is detected in distal leaves, demonstrating a systemic induction of resistance by a root-endophytic fungus. The systemically altered "defense readiness" is associated with an elevated antioxidative capacity due to an activation of the glutathione-ascorbate cycle and results in an overall increase in grain yield. Because P. indica can be easily propagated in the absence of a host plant, we conclude that the fungus could be exploited to increase disease resistance and yield in crop plants.     

Interface connections of a transmembrane voltage sensor

Voltage-sensitive ion channels open and close in response to changes in transmembrane (TM) potential caused by the motion of the S4 voltage sensors. These sensors are alpha-helices that include four or more positively charged amino acids, most commonly arginine. The so-called paddle model, based on the high-resolution structure of the KvAP K+ channel [Jiang, et al. (2003) Nature 423, 33-41], posits that the S4 sensors move within the membrane bilayer in response to TM voltage changes. Direct exposure of S4 sensors to lipid is contrary to the classical expectation that the dielectric contrast between the membrane hydrocarbon core and water presents an insurmountable energetic penalty to burial of electric charges. Nevertheless, recent experiments have shown that a helix with the sequence of KvAP S4 can be inserted across the endoplasmic reticulum membrane. To reconcile this result with the classical energetics argument, we have carried out a molecular dynamics simulation of an isolated TM S4 helix in a lipid bilayer. The simulation reveals a stabilizing hydrogen-bonded network of water and lipid phosphates around the arginines that reduces the effective thickness of the bilayer hydrocarbon core to approximately 10 A in the vicinity of the helix. It suggests that bilayer phospholipids can adapt locally to strongly perturbing protein elements, causing the phospholipids to become a structural extension of the protein.